Influence of daily setup measurements and corrections on the estimated delivered dose during IMRT treatment of prostate cancer patients.

PURPOSE: To evaluate the impact of marker-based position verification, using daily imaging and an off-line correction protocol, by calculating the delivered dose to prostate, rectum and bladder. METHODS: Prostate cancer patients (n=217) were treated with IMRT, receiving 35 daily fractions. Plans with five beams were optimized taking target coverage (CTV, boost) and organs-at-risk (rectum and bladder) into account. PTV margins were 8mm. Prostate position was verified daily using implanted fiducial gold markers by imaging the first segment of all the five beams on an EPID. Setup deviations were corrected off-line using an adapted shrinking-action-level protocol. The estimated delivered dose, including daily organ movements, was calculated using a version of PLATO's dose engine, enabling batch processing of large numbers of patients. The dose was calculated +/- inclusion of setup corrections, and was evaluated relative to the original static plan. The marker-based measurements were considered representative for all organs. RESULTS: Daily organ movements would result in an underdosage of 2-3Gy to CTV and boost volume relative to the original plan, which was prevented by daily setup corrections. The dose to rectum and bladder was on average unchanged, but a large spread was introduced by organ movements, which was reduced by including setup corrections. CONCLUSIONS: Without position verification and setup corrections, margins of 8mm would be insufficient to account for position uncertainties during IMRT of prostate cancer. With the daily off-line correction protocol, the remaining variations are accommodated adequately.

Results of hematopoietic stem cell transplantation after treatment with different high-dose total-body irradiation regimens in five Dutch centers.

PURPOSE: To evaluate results of high-dose total-body irradiation (TBI) regimens for hematopoietic stem cell transplantation. METHODS AND MATERIALS: A total of 1,032 patients underwent TBI in one or two fractions before autologous or allogeneic hematologic stem cell transplantation for acute leukemia and non-Hodgkin's lymphoma. The TBI regimens were normalized by using the biological effective dose (BED) concept. The BED values were divided into three dose groups. Study end points were relapse incidence (RI), non-relapse mortality (NRM), relapse-free survival (RFS), and overall survival (OS). Multivariate analysis was performed, stratified by disease. RESULTS: In the highest TBI dose group, RI was significantly lower and NRM was higher vs. the lower dose groups. However, a significant influence on RFS and OS was not found. Relapses in the eye region were found only after shielding to very low doses. Age was of significant influence on OS, RFS, and NRM in favor of younger patients. The NRM of patients older than 40 years significantly increased, and OS decreased. There was no influence of age on RI. Men had better OS and RFS and lower NRM. Type of transplantation significantly influenced RI and NRM for patients with acute leukemia and non-Hodgkin's lymphoma. There was no influence on RFS and OS. CONCLUSIONS: Both RI and NRM were significantly influenced by the size of the BED of single-dose or two-fraction TBI regimens; OS and RFS were not. Age was of highly significant influence on NRM, but there was no influence of age on RI. Hyperfractionated TBI with a high BED might be useful, assuming NRM can be reduced.

Intrafraction motion of the prostate during external-beam radiation therapy: analysis of 427 patients with implanted fiducial markers.

PURPOSE: To analyze the intrafraction motion of the prostate during external-beam radiation therapy of patients with prostate cancer. METHODS AND MATERIALS: Between August 2001-December 2005, 427 patients with Stage T3Nx/0Mx/0 prostate carcinoma received intensity-modulated radiation therapy treatment combined with position verification with fiducial gold markers. For a total of 11,426 treatment fractions (average, 27 per patient), portal images were taken of the first segment of all five beams. The irradiation time of the technique varied between 5-7 min. From these data, the location of gold markers could be established within every treatment beam under the assumption of minimal marker movement. RESULTS: In 66% of treatment fractions, a motion outside a range of 2 mm was observed, with 28% outside a range of 3 mm. The intrafraction marker movements showed that motion directions were often reversed. However, the effect was small. Even with perfect online position-correction at the start of irradiation, intrafraction motion caused position uncertainty, but systematic errors (Sigma) were limited to <0.6 mm, and random errors (sigma) to <0.9 mm. This would result in a lower limit of 2 mm for margins, in the absence of any other uncertainties. CONCLUSIONS: Intrafraction motion of the prostate occurs frequently during external-beam irradiation on a time scale of 5-7 min. Margins of 2 mm account for these intrafraction motions. However, larger margins are required in practice to accommodate other uncertainties in the treatment.

Analysis of fiducial marker-based position verification in the external beam radiotherapy of patients with prostate cancer.

PURPOSE: Evaluate the fiducial marker-based position verification in the external-beam radiotherapy of patients with prostate cancer. METHODS: Four hundred and fifty-three patients with prostate cancer received an IMRT treatment combined with fiducial marker-based position verification. Portal images were taken in all 35 treatment fractions. This database was used to study the accuracy of detecting the prostate position as well as the presence of time trends and the effectiveness of commonly used off-line correction protocols. RESULTS: The variation in inter-marker distance shows that the prostate position can be detected with an accuracy better than 0.6 mm. Significant time trends in prostate position occurred in 35%, 18% and 48% of the patients in the vertical, lateral and longitudinal directions, respectively, with 34%, 9% and 35% deviating more than 3 mm over the course of the treatment. Off-line correction protocols that estimate a deviation only in the first fractions of the treatment (shrinking action level (SAL), no action level (NAL)) are not effective in following these trends. With daily off-line position correction using an adapted SAL protocol we reduced systematic positioning errors in clinical practice to less than 0.8 mm in all directions. CONCLUSION: Fiducial markers are a reliable tool for prostate position verification. Time trends occur frequently. Correction procedures must take such trends into account.

Loco-regional conformal radiotherapy of the breast: delineation of the regional lymph node clinical target volumes in treatment position.

BACKGROUND AND PURPOSE: As the location of the regional lymph nodes (LNs) of the breast varies largely between patients and may be dependant on the position of the arm, adequate localization of these nodes is mandatory in order to fully take advantage of optimized conformal radiotherapy. For this purpose, the anatomical boundaries of the regional lymph node (LN) clinical target volumes (CTVs) for delineation on transverse CT-slices, made in treatment position, were established. PATIENTS AND METHODS: Anatomical and surgical descriptions of the regional LNs of the breast, as well as a shoulder dissection, were studied. Axial slices of a human cadaver with one arm in abduction and the other in adduction were investigated, to assess the displacement of LNs by abduction of the arm into treatment position. Based on these findings, we defined the anatomical boundaries of the regional LN CTVs visible on transverse CT-slices. RESULTS: Standard anatomical and surgical descriptions appeared to be inadequate for determination of the boundaries of the regional LN CTVs in treatment position. With abduction of the arm, a change in position of all regional LNs, except for the medial supraclavicular LNs and internal mammary LNs, was observed in the anatomical cross-sections. This was also taken into account in our delineation protocol proposal. CONCLUSIONS: Anatomically based guidelines for delineation of the regional LN CTVs for loco-regional irradiation of the breast on transverse CT-slices, made in treatment position, have been developed in this study. These could be used as a basis for conformal radiotherapy.

Clinical feasibility study for the use of implanted gold seeds in the prostate as reliable positioning markers during megavoltage irradiation.

BACKGROUND AND PURPOSE: The aim of this study was to assess the feasibility of using gold seed implants in the prostate for position verification, using an a-Si flat panel imager as a detector during megavoltage irradiation of prostate carcinoma. This is a study to guarantee positioning accuracy in intensity-modulated radiotherapy. METHODS AND MATERIALS: Ten patients with localized prostate carcinoma (T2-3) received between one and three fiducial gold markers in the prostate. All patients were treated with 3-D conformal radiotherapy with an anterior-posterior (AP) and two lateral wedge fields. The acute gastrointestinal (GI) and genitourinary (GU) toxicities were scored using common toxicity criteria scales (CTC). Using three consecutive CT scans and portal images obtained during the treatment we have studied the occurrence of any change in prostate shape (deformation), seed migration and the magnitude of translations and rotations of the prostate. RESULTS: We observed no acute major complications for prostate irradiation regarding the seed implantation. The maximum acute GU toxicity grade 2 (dysuria and frequency) was observed in seven patients during the treatment. The maximum grade 2 (diarrhoea) was scored in two patients regarding the acute GI toxicities. No significant prostate deformation could be detected in the consecutive CT scans. It appeared that the distances between the markers only slightly changed during treatment (S.D. 0.5 mm). Random prostate translations were (1 S.D.) 2.1, 3.2 and 2.2 mm in the lateral (LR), AP and cranial-caudal (CC) directions, respectively, whereas systematic translations were 3.3, 4.8 and 3.5 mm in the LR, AP and CC directions, respectively. Random prostate rotations were (1 S.D.) 3.6, 1.7 and 1.9 degrees around the LR, AP and CC axis, respectively, whereas systematic rotations were 4.7, 2.0 and 2.7 degrees around the LR, AP and CC axis, respectively. CONCLUSIONS: We found that the fiducial gold seeds are a safe and appropriate device to verify and correct the position of prostate during megavoltage irradiation. The amount of seed migration and prostate deformation is far below our present tumour delineation accuracy.

Comparison of megavoltage position verification for prostate irradiation based on bony anatomy and implanted fiducials.

PURPOSE: The patient position during radiotherapy treatment of prostate cancer can be verified with the help of portal images acquired during treatment. In this study we quantify the clinical consequences of the use of image-based verification based on the bony anatomy and the prostate target itself. PATIENTS AND METHODS: We analysed 2025 portal images and 23 computed tomography (CT) scans from 23 patients with prostate cancer. In all patients gold markers were implanted prior to CT scanning. Statistical data for both random and systematic errors were calculated for displacements of bones and markers and we investigated the effectiveness of an off-line correction protocol. RESULTS: Standard deviations for systematic marker displacement are 2.4 mm in the lateral (LR) direction, 4.4 mm in the anterior-posterior (AP) direction and 3.7 mm in the caudal-cranial direction (CC). Application of off-line position verification based on the marker positions results in a shrinkage of the systematic error to well below 1 mm. Position verification based on the bony anatomy reduces the systematic target uncertainty to 50% in the AP direction and in the LR direction. No reduction was observed in the CC direction. For six out of 23 patients we found an increase of the systematic error after application of bony anatomy-based position verification. CONCLUSIONS: We show that even if correction based on the bony anatomy is applied, considerable margins have to be set to account for organ motion. Our study highlights that for individual patients the systematic error can increase after application of bony anatomy-based position verification, whereas the population standard deviation will decrease. Off-line target-based position verification effectively reduces the systematic error to well below 1 mm, thus enabling significant margin reduction.

Surgery as part of combined modality treatment in stage IIIB non-small cell lung cancer.

BACKGROUND: The role of surgery after neoadjuvant chemotherapy in patients with stage IIIB non-small cell lung cancer (NSCLC) remains unclear. METHODS: A prospective multicenter trial of neoadjuvant chemotherapy followed by surgery or radiotherapy or both was conducted with 41 patients with stage IIIB NSCLC. End points were toxicity, response, downstaging, complete resectability, and survival. The diagnostic value of repeat mediastinoscopy after neoadjuvant chemotherapy (three courses of gemcitabine/cisplatin) was also studied. RESULTS: Response rate after neoadjuvant chemotherapy was 66% (27 of 41). Fifteen patients underwent repeat mediastinoscopy, which proved to be inadequate in 6 patients. Two repeat mediastinoscopies were false negative. Resection was performed in 18 patients, of which 10 proved to be radical. Hospital mortality was 2.4% (n = 1). Major complications occurred in 6 patients (fistula, empyema, hemorrhage). Histopathologically proven downstaging was seen in 16 patients (39%). Twenty-five patients underwent radiotherapy of whom 14 were diagnosed with stable/progressive disease and 9 with partial/complete response. Median survival for all patients was 15.1 months, for nonresponders 8.4 months and for responders 16.8 months (p = 0.11). Patients with partial/complete response had a mean survival of 21.5 months after resection and 13.0 months after radiotherapy (p = 0.0003). CONCLUSIONS: Radical surgery can be performed in 37% (10 of 27) of the responders resulting in a prolonged survival. Surgery as part of combined modality treatment is feasible in stage IIIB NSCLC. Results of a repeat mediastinoscopy are disappointing and proved to be a not-so-effective restaging tool because of the high number of incomplete procedures and because it yields false negative results.

Measurements and clinical consequences of prostate motion during a radiotherapy fraction.

PURPOSE: Here we study the magnitude of prostate motion during the delivery of a radiotherapy fraction. These motions have clinical consequences for on-line position verification and the choice of margins around the target volume. METHODS AND MATERIALS: We studied the motion of the prostate for 10 patients during 251 radiotherapy treatment fractions by assessing the position of implanted gold markers. Gold markers of 1 mm diameter and 5 mm length were implanted in the prostate before the start of the radiotherapy. We obtained movies during each fraction using an a-Si flat-panel imager. The markers could be detected in separate frames using a marker extraction kernel. RESULTS: Marker displacements as large as 9.5 mm were detected in one fraction. The motion of the prostate is greatest in the caudal-cranial and the anterior-posterior directions. Within a time window of 2 to 3 min, deviations from the initial marker position, averaged over all patients, are 0.3 +/- 0.5 mm and -0.4 +/- 0.7 mm in the anterior-posterior and caudal-cranial directions, respectively. CONCLUSIONS: It appeared that on average, the intrafraction prostate motions did not result in margins larger than 1 mm, provided that the position verification is performed at time intervals of 2 to 3 min. Only for some patients performing more frequent position verification or adding extra margins of 2 to 3 mm is required to account for intrafraction prostate motions.